TY - JOUR
T1 - Fibrin microbeads (FMB) as a 3D platform for kidney gene and cell therapy
AU - Shimony, N.
AU - Gorodetsky, R.
AU - Marx, G.
AU - Gal, D.
AU - Rivkin, R.
AU - Ben-Ari, Alon
AU - Landsman, A.
AU - Haviv, Y. S.
PY - 2006/2/1
Y1 - 2006/2/1
N2 - Cell and gene therapy may alter the outcome of renal diseases, such as hereditary nephropathies, acute and chronic glomerulonephritis and allograft nephropathy. However, owing to blockade of many viral and cellular vehicles by the complex glomerular architecture, the exact nature of gene and cell delivery into specific renal compartments remains currently unknown. To study the interaction of viral vectors with a variety of renal cells and mesenchymal stem cells (MSCs), we employed a novel biological three-dimensional (3D) matrix comprised of fibrin microbeads (FMB) in comparison to monolayer cell culture. Our studies showed that renal cells of both established and primary lines can grow efficiently on FMB and differentiate into epithelial structures, as shown by electron microscopy. Gene delivery into renal cells in 3D was observed for several viral vectors and growth in 3D on FMB conferred resistance to renal cancer cells in the context of oncolytic adenoviruses. Finally, MSCs from various rodent species attached to FMB, grew robustly, survived for several weeks and could efficiently be transduced on FMB. Thus, on the basis of growth, differentiation and transduction of renal cells in 3D, FMB emerge as a novel 3D cellular microenvironment that differs substantially from monolayer cell cultures.
AB - Cell and gene therapy may alter the outcome of renal diseases, such as hereditary nephropathies, acute and chronic glomerulonephritis and allograft nephropathy. However, owing to blockade of many viral and cellular vehicles by the complex glomerular architecture, the exact nature of gene and cell delivery into specific renal compartments remains currently unknown. To study the interaction of viral vectors with a variety of renal cells and mesenchymal stem cells (MSCs), we employed a novel biological three-dimensional (3D) matrix comprised of fibrin microbeads (FMB) in comparison to monolayer cell culture. Our studies showed that renal cells of both established and primary lines can grow efficiently on FMB and differentiate into epithelial structures, as shown by electron microscopy. Gene delivery into renal cells in 3D was observed for several viral vectors and growth in 3D on FMB conferred resistance to renal cancer cells in the context of oncolytic adenoviruses. Finally, MSCs from various rodent species attached to FMB, grew robustly, survived for several weeks and could efficiently be transduced on FMB. Thus, on the basis of growth, differentiation and transduction of renal cells in 3D, FMB emerge as a novel 3D cellular microenvironment that differs substantially from monolayer cell cultures.
KW - Fibrin
KW - Kidney cell therapy
KW - Kidney gene therapy
UR - http://www.scopus.com/inward/record.url?scp=31544470632&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=31544470632&partnerID=8YFLogxK
U2 - 10.1038/sj.ki.5000099
DO - 10.1038/sj.ki.5000099
M3 - Article
C2 - 16395256
AN - SCOPUS:31544470632
VL - 69
SP - 625
EP - 633
JO - Kidney International
JF - Kidney International
SN - 0085-2538
IS - 3
ER -